A principal obstacle to the study of osteoarthritis (OA) and its treatment has been the lack of reliable methods for detecting early disease and for monitoring its progression and response to treatment. In this study, we propose the use of magnetic resonance imaging (MRI) to detect and monitor early disease and for monitoring its progression and response to treatment. In this study, we propose the use of magnetic resonance imaging (MRI) to detect and monitor early signs of OA in a population at high risk of developing the disease within the three-year study period. Our objective is to evaluate the utility of MRI for predicting future cartilage loss and the development of OA. Recently developed MRI techniques and 3-dimensional (3D) Image processing methods allow detection and quantification of early changes in cartilage which may indicate future progression to OA. The volumes of individual articular cartilage plates in the knee may be accurately and reproducibly quantified by MRI. Longitudinal monitoring of cartilage volume may allow detection of cartilage loss before patients develop radiographic signs of QA. Even before cartilage loss occurs, T2-weighted MRI can identify diseased cartilage by increased signal intensity resulting from collagen matrix damage and elevated water content. Cartilage water content may be quantified accurately in vivo, using true proton density maps generated from MR images corrected for T1- and T2-relaxation. These MR techniques may allow patients at greatest risk for QA to be identified early in the course of the disease, when there is potentially greater change for favorable therapeutic outcome. Longitudinal evaluation of these MR- measured parameters may permit quantification of the rate of disease progression as well as the response to therapy. In clinical studies of anti-arthritic therapies, this capability would permit greater objectivity and reproducibility in evaluations of disease activity and treatment response than is currently possible with available clinical, laboratory or radiographic methodology. This study will follow 50 subjects who initially lack evidence of QA, but who recently underwent meniscal surgery and are therefore at high risk for developing OA of the knee within the subsequent 3 years. Subjects will receive MRI of the knee using the three techniques described above, at 2 months post-surgery and then every 12 months for 3 years. Scintigraphic, radiographic and clinical evaluation of the knee will be performed at the same time points as MRI. Changes In femorotiblal cartilage volume will be quantified at each visit using a previously validated MRI method, and correlated with scintigraphy and the subsequent development of radiographic and clinical abnormalities of OA. The study will also test whether the MRI-measured fractional water content of cartilage, and the extent of cartilage involvement by high signal abnormalities on T2-weighted MRI, are predictors of the degree of cartilage loss observed on subsequent evaluations. The MRI techniques described here would be a valuable adjunct to therapeutic trials of potential treatments of OA, and offer an intriguing new research tool with which to study the pathophysiology of this disease.
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